A role for leukotrienes in cyclosporine nephrotoxicity

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Presentation transcript:

A role for leukotrienes in cyclosporine nephrotoxicity David W. Butterly, Robert F. Spurney, Phillip Ruiz, Robert Griffiths, Christine Albrightson, Thomas M. Coffman Kidney International Volume 57, Issue 6, Pages 2586-2593 (June 2000) DOI: 10.1046/j.1523-1755.2000.00118.x Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 1 The 5-lipoxygenase (5-LO) pathway of arachidonic acid (AA) metabolism. Kidney International 2000 57, 2586-2593DOI: (10.1046/j.1523-1755.2000.00118.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 2 Effects of peptidoleukotriene receptor blockade on renal histopathological changes in rats treated with cyclosporine A (CsA). (A) Representative photomicrograph of an HE-stained section of a renal isograft from a rat that was treated with CsA 50 mg/kg/day for six days. The major structural abnormality in these kidneys is diffuse vacuolization of proximal tubule cells that can been seen throughout the section. (B) A similarly stained section of a renal isograft from a rat that received CsA along with the peptidoleukotriene receptor antagonist SKF106203. Kidney histomorphology was virtually normal in these animals and not significant from that of renal isografts from animals that never received CsA (data not shown). Kidney International 2000 57, 2586-2593DOI: (10.1046/j.1523-1755.2000.00118.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 3 Histopathological grading of rat renal isograft sections. The severity of the histopathological abnormalities observed in renal isografts from the experimental groups were graded as described. The degree of histopathological abnormality was significantly reduced in the group that received CsA + SKF 106203 (▪) compared with the group that received CsA alone (□). Moreover, there was no significant difference in histopathological score between the group that received CsA + SKF 106203 and the group that received olive oil vehicle without CsA () (*P < 0.01). Kidney International 2000 57, 2586-2593DOI: (10.1046/j.1523-1755.2000.00118.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 3 Histopathological grading of rat renal isograft sections. The severity of the histopathological abnormalities observed in renal isografts from the experimental groups were graded as described. The degree of histopathological abnormality was significantly reduced in the group that received CsA + SKF 106203 (▪) compared with the group that received CsA alone (□). Moreover, there was no significant difference in histopathological score between the group that received CsA + SKF 106203 and the group that received olive oil vehicle without CsA () (*P < 0.01). Kidney International 2000 57, 2586-2593DOI: (10.1046/j.1523-1755.2000.00118.x) Copyright © 2000 International Society of Nephrology Terms and Conditions